Introduction

• Pyrrolizidine alkaloids are toxins which mainly cause hepatotoxicity and liver failure but may also cause respiratory disease and renal damage depending on the plants involved.
• Cause: pyrrolizidine alkaloids are produced by 3 main plant families:
  • Asteraceae (Senecio spp, tansy ragwort).
  • Tobaceae (Crotalaria spp, rattlebox).
  • Boraginaceae (Heliotropum, Amsinckia, Trichodesma and Echium spp).
• Signs: anorexia, weight loss, ventral edema, depression, icterus +/- signs of hepatic encephalopathy, eg apparent blindness, circling, head-pressing; respiratory distress.
• Diagnosis: liver function tests, hepatic biopsy, liver enzymes, alkaloids in liver, necropsy.
• Treatment: no effective specific treatment.
• Prognosis: poor if recurrent or severe.

Pathogenesis

Etiology

• Pyrrolizidine alkaloids produced by plants.
• Ragwort (Senecio jacobea) - contains 8 alkaloids, including retrorsine.
• Heliotrope contains several alkaloids, including lasiocarpine and heliotrine.
• Crotalaria spp contain mainly monocrotaline, some also contain fulvine and crispatine.

Predisposing factors

General

• Plants containing pyrrolizidine alkaloids are usually, but not always, unpalatable and mostly ignored.
• May be consumed when there is little alternative feed.
• Dead ragwort and other pyrrolizidine alkaloid plants, eg in hay, are more palatable.
• Repeated ingestion of small amounts over several seasons may → disease - cumulative effect.

Pathophysiology

• Pyrrolizidine alkaloids have primary toxic effect on hepatic parenchyma and secondary effects on hepatic veins, pulmonary tissues and other extrahepatic tissues such as the lungs, kidneys and heart.
• Clinical signs occur once liver damage has progressed sufficiently to compromise liver function.
• Alkaloids → primary toxic effect on liver parenchyma → megalocytosis → necrosis and inhibition of cell division.
• Reactive alkaloids crosslink DNA, impair cell division and may affect protein synthesis.
• Can interfere with copper excretion.
• Secondary toxic effect on centrilobular and hepatic veins → endothelial damage and perivascular fibrosis → vascular occlusion.
• Apparent sudden onset, often weeks after ingestion has stopped → hepatic encephalopathy Liver: hepatoencephalopathy.

Timecourse

• Usually chronic.
• Liver damage may accumulate over several years.
• Onset of clinical signs may occur several weeks to months after ingestion of plant has stopped.

Epidemiology

• Plants are not usually palatable, therefore ignored unless food is scarce.
• Dead plants, eg in hay, are readily eaten.
• Toxicity is cumulative; liver damage may occur over several seasons.

Diagnosis

Treatment

Prevention

Outcomes